Compositions for intravenous infusion of istaroxime, or a metabolite of istaroxime, in human patients suffering from heart failure are disclosed. Likewise, methods for extended infusion of istaroxime or its metabolites in individuals with heart failure are disclosed. In particular, some methods disclosed herein include the infusion of istaroxime, or a metabolite thereof, for a period of time that is greater than six hours in order to improve cardiac relaxation without triggering arrhythmogenic events in an individual suffering from heart failure. Other methods include administration of istaroxime until certain plasma concentration thresholds of istaroxime metabolites are achieved. Also disclosed are istaroxime metabolites with selective SERCA2a activation.

Compositions for intravenous infusion of istaroxime, or a metabolite of istaroxime, in human patients suffering from heart failure are disclosed. Likewise, methods for extended infusion of istaroxime or its metabolites in individuals with heart failure are disclosed. In particular, some methods disclosed herein include the infusion of istaroxime, or a metabolite thereof, for a period of time that is greater than six hours in order to improve cardiac relaxation without triggering arrhythmogenic events in an individual suffering from heart failure. Other methods include administration of istaroxime until certain plasma concentration thresholds of istaroxime metabolites are achieved. Also disclosed are istaroxime metabolites with selective SERCA2a activation.

Disclosed herein are peptide sequences capable of directing adeno-associated viruses (AAV) to target specific environments, for example the nervous system and the heart, in a subject. Also disclosed are AAVs having non-naturally occurring capsid proteins comprising the disclosed peptide sequences, and methods of using the AAVs to treat diseases.

Methods and small molecule compounds for inhibition of sodium channels are provided. One example of a class of compounds that may be used is represented by the compound of Formula (I) or a pharmaceutically acceptable salt, N-oxide or solvate thereof, wherein A, B, D, R, R.sub.1, R′.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 are as described herein.

Methods and small molecule compounds for inhibition of sodium channels are provided. One example of a class of compounds that may be used is represented by the compound of Formula (I) or a pharmaceutically acceptable salt, N-oxide or solvate thereof, wherein A, B, D, R, R.sub.1, R′.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 are as described herein.

A method for treating arrythmia in subject in need thereof, which includes administering to the subject a therapeutically effective amount of the compound of formula (I) or a pharmaceutically acceptable salt and/or solvate thereof;

##STR00001##

in which X, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, Y, and are as described in the claims.

A method for treating arrythmia in subject in need thereof, which includes administering to the subject a therapeutically effective amount of the compound of formula (I) or a pharmaceutically acceptable salt and/or solvate thereof;

##STR00001##

in which X, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, Y, and are as described in the claims.

The present disclosure relates to crystalline solid forms of a stimulator of soluble guanylate cyclase (sGC), Compound I: ##STR00001##
Also provided herein are methods for the preparation of these solid forms. The invention also relates to pharmaceutical formulations and dosage forms comprising these solid forms and their uses thereof, alone or in combination with one or more additional agents, for treating and/or preventing various diseases or disorders; these diseases or disorders are ones that may benefit from sGC stimulation or from an increase in the concentration of nitric oxide (NO) and/or cyclic guanosine monophosphate (cGMP).

The invention provides compositions and methods for providing a cardioprotective effect in a subject. Specifically, the invention relates to compositions and methods for treating cardiovascular ailments, such as compositions and methods for attenuating or ameliorating the development of cardiac contractile dysfunction, myocardial fibrosis or maladaptive remodeling in a subject having or having had a myocardial infarction (MI) or at risk of having a myocardial infarction by administering a retinoic acid receptor-beta (RARβ) agonist.

The invention provides compositions and methods for providing a cardioprotective effect in a subject. Specifically, the invention relates to compositions and methods for treating cardiovascular ailments, such as compositions and methods for attenuating or ameliorating the development of cardiac contractile dysfunction, myocardial fibrosis or maladaptive remodeling in a subject having or having had a myocardial infarction (MI) or at risk of having a myocardial infarction by administering a retinoic acid receptor-beta (RARβ) agonist.